Seeking NIH to fund studies on medical ethics, conflicts of interest in medicine and research, and prescribing behavior

Adriane Fugh-Berman MD is principal investigator (PI) of the PharmedOut project. PharmedOut is an independent, publicly funded Georgetown University Medical Center project that educates physicians about industry influence on prescribing. project that empowers physicians to identify and counter inappropriate pharmaceutical promotion practices. PharmedOut promotes evidence-based medicine by providing news, resources, and links to pharma-free CME courses.

PharmedOut is requesting that the U.S. NIH (National Institutes of Health) fund more research into ethics, conflicts of interest, and prescribing behavior. One hundred researchers, clinicians, and ethicists have signed a letter sponsored by PharmedOut asking NIH to fund research on medical ethics, conflicts of interest, and industry influence on prescribing behavior. Stimulus funds have increased the NIH budget by ten billion dollars, but NIH has no mechanism for funding research on how commercial interests affect the choice of medical therapeutics.

Signers include Virginia Barbour MD, Chief Editor of PLoS Medicine, Jerome Kassirer, MD, former editor in chief of the New England Journal of Medicine, Jerry Avorn MD, the Harvard physician who invented academic detailing, Kay Dickersin PhD, Director of the U.S. Cochrane Center, and Susan Wood, PhD, former head of the FDA Office of Women’s Health Research, who resigned over political influence regarding FDA decisions on the emergency contraceptive Plan B. Institutional signers include the Public Library of Science, the American Medical Student Association, the National Physicians Alliance, Consumers Union, the Center for Science in the Public Interest, and the National Women’s Health Network.

The letter, sent to NIH today, is available at http://www.pharmedout.org/NIHLetter.pdf (PDF) and below:

Nov. 17, 2009

From: Adriane Fugh-Berman MD
Department of Physiology and Biophysics
Georgetown University Medical Center
Box 571460
Washington DC 20057-1460
Phone: (202) 687-7845
Fax: (202) 687-7407
ajf29 AT georgetown DOT edu

To: Francis S. Collins, MD, PhD
Director
National Institutes of Health
9000 Rockville Pike
Bethesda, MD 20892

Dear Dr. Collins,

We are writing to ask NIH to fund studies on medical ethics, conflicts of interest in medicine and research, and prescribing behavior. NIH funds a substantial portion of the generation and dissemination of evidence, but the uptake of that evidence and its translation into clinical practice is strongly affected by the complex web of relationships that exists among industry, academicians, medical educators and clinicians.

There is growing evidence that each strand of this web is compromised by ethical lapses and financial conflicts of interest. The recent disclosure of ghostwritten articles, physician payoffs, and the use of academic opinion leaders to increase markets for FDA-regulated products indicate that ethical lapses may permeate biomedical research. A PLoS Medicine editorial in September called ghostwriting “The dirty little secret of medical publishing” and notes “the systematic manipulation and abuse of scholarly publishing by the pharmaceutical industry and its commercial partners in their attempt to influence the health care decisions of physicians and the general public.” [1] An October 1 editorial in the Boston Globe called for a ban on industry speaker fees to physicians. [2] Last month, a commentary in JAMA called for physicians to pay for continuing medical education (CME), [3] citing a recent Institute of Medicine report [4] that criticized physicians’ reliance on industry-funded education.

A stated goal of the NIH is to “exemplify and promote the highest level of scientific integrity, public accountability, and social responsibility in the conduct of science.” Could the muted effect that large, definitive NIH studies, including the WHI, ALLHAT, and CATIE, have had on clinical practice be due to commercial influences? To what extent have ghostwritten articles corrupted the medical and scientific literature? The extent to which industry influences the interpretation of science is unknown.

Dr. Elias Zerhouni, in the September 17th issue of Nature, commenting on Senator Grassley’s investigation of academic medical centers, said “People flouted the rules, didn’t disclose, and did it for years on end, repeatedly.” [5]

In your role as the director of “the steward of medical and behavioral research for the Nation,” we ask that you acknowledge the research gap on the effect of conflicts of interest and commercial influence on medical decisionmaking and set in motion a process that leads to recognition of the importance of funding studies on research ethics, the beliefs and behaviors of researchers and clinicians, and the effects of industry-academic relationships on the generation and dissemination of medical knowledge.

Between bench and bedside lies a path treacherous with ethical quandaries. NIH is the best place to launch and support a scientifically rigorous inquiry into the state of research ethics, industry-academic relationships, and the effect of these relationships on human health. There is currently no identifiable mechanism through which NIH would fund this research.

Your leadership regarding the importance of this issue as one the NIH needs to direct resources towards is essential. We hope to discuss these issues in a face-to-face meeting.

Sincerely,

Adriane Fugh-Berman, MD
Associate Professor, Georgetown University Medical Center
Director, PharmedOut

ajf29 AT georgetown DOT edu
http://pharmedout.org

[and others whose signatures can be seen at the PDF - ed.]

[1] Ghostwriting: The Dirty Little Secret of Medical Publishing That Just Got Bigger. PLoS Medicine, September 8, 2009. http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1000156

[2] Keep Doctors Independent; Ban Fees From Drug Makers. Boston Globe, October 1, 2009. http://www.boston.com/bostonglobe/editorial_opinion/editorials/articles/2009/10/01/keep_doctors_independent_ban_fees_from_drug_makers/

[3] Campbell EG, Rosenthal M. Reform of Continuing Medical Education: Investments in Physician Human Capital. JAMA. 2009;302(16):1807-1808.
http://jama.ama-assn.org/cgi/content/full/302/16/1807?home

[4] Institute of Medicine. Conflict of Interest in Medical Research, Education, and Practice. Washington, DC: National Academies Press; April 28, 2009. http://www.iom.edu/CMS/3740/47464/65721.aspx

[5] Wadman M. The Senator’s sleuth. Nature. 2009 Sept;461(17):330-4.

This letter caught my eye, and I expressed support as follows, adding an additional angle to Dr. Fugh-Berman's letter:

Dear Dr. Fugh-Berman,

As a blogger at Healthcare Renewal, I will enthusiastically sign on to and endorse your letter calling on NIH to fund more research into ethics, conflicts of interest, and prescribing. I also wish to add an extended point:

The issues of ethics and conflict of interest also affect healthcare information technology (HIT), and ultimately physician practice. HIT applications are experimental medical devices now being pushed upon physicians via the Office of the National Coordinator and HHS. These medical devices are soon to undergo regulation as such in the EU (pdf report from the Swedish Medical Products Agency here), Canada, the U.S. and other countries as well.

They are used in patient care without patient consent. Their use holds significant potential to monitor and enforce practices deemed appropriate by whomever has the most influence on the bodies controlling the use of these technologies and the data they generate.

From that perspective, and from the perspective of the 2009 National Research Council report that calls for accelerating interdisciplinary research in biomedical informatics, computer science, social science [i.e., the social and ethical implications of health IT], and health care engineering as a sine qua non of health IT success, I believe it is time for NIH to take a leadership role in regulating these devices, conflicts of interest in the health IT industry, and the ethics of their use.

I perhaps should have written "I believe it is time for NIH to take a leadership role in sponsoring research on regulating these devices, conflicts of interest in the health IT industry, and the ethics of their use", rather than calling on NIH to be a regulator. However, until the regulatory affairs concerning health IT are in order, I felt the stronger statement appropriate.

-- SS

The Editorial that Wasn't: Evidence for Systematic Research Manipulation Undetectable by Critical Review

Woe to those of us who have been advocates for evidence-based medicine.  A short description of the evidence-based medicine is medicine whose practice is informed by critical, rigorous review of the best available evidence from clinical research as revealed by systematic search of the published research literature, as well as by the clinician's understanding of biology and the medical and biopsychosocial context, and by the patient's own values.

Evidence-based medicine is based on some key assumptions.  One is that a systematic review will reveal all the results of research studies that are relevant to the issue at hand.  A second is that while the research studies may be flawed and imperfect, they are reported honestly.

Unfortunately, as we have repeatedly discussed, there is more and more evidence that a systematic review will not reveal all relevant results, because research studies may be suppressed, perhaps often, when their results are unfavorable to vested interests.  (Look here for further discussion.)  There is also considerable anecdotal evidence that the design, implementation, and analysis of research studies may be manipulated to make the results more likely to favor vested interests.  (Look here for further discussion.)

An article by Vedula et al just published in the renowned New England Journal of Medicine suggests that such manipulation might be systemic, and that the reporting of manipulated studies may not clearly show what manipulation was done. (1)

To summarize, the authors got access through legal proceedings to internal study protocols and research reports from clinical trials sponsored by Parke-Davis (later merged into Pfizer Inc) of gabapentin (Neurontin) for a variety of clinical problems other than seizures.  Gabapentin was originally marketed as an anti-seizure drug, but Pfizer later "admitted guilt for off-label marketing."  (We discussed the stealth marketing campaign for Neurontin here.)  Vedula et al compared the primary outcome variables specified in the original research protocols, internal research reports, and any publications of the trials' results.  They identified 21 trials, 13 of which were published.  For 12 of the 13, the authors had access to the internal protocol, report, or both.  The main results were:

For 8 of the 12 published trials, there was a disagreement between the definition of the primary outcome in the protocol and that in the published report.... Sources of disagreement included the introduction of an entirely new primary outcome in the published report (in the case of 6 trials); failure to distinguish between primary and secondary outcomes in the published report, even though the protocol did distinguish between them (2 trials); relegation of a primary outcome in the protocol to a secondary outcome in the published report (2 trials); and failure to include in the published report one or more primary outcomes specified in the protocol (5 trials).

Furthermore, it appeared that failure of published articles to clearly and fully report results in terms of the original, pre-specified primary outcome variables occurred when these comparisons were not favorable to gabapentin. As the authors summarized:

Thus, trials with findings that were not statistically significant (P≥0.05) for the protocol-defined primary outcome, according to the internal documents, either were not published in full or were published with a changed primary outcome.

As shown in Figure 3, all the changes that took place between what was specified in the protocol, what was known before publication (as presented in the internal company research reports), and what was reported to the public led to a more favorable presentation in the medical literature of gabapentin's efficacy for unapproved indications.

They concluded:

We are concerned that the reporting practices observed in our analysis do not meet the ethical standards for clinical research or maintain the integrity of scientific knowledge. Fair and honest treatment of patients enrolled in clinical trials of any kind requires full, open, and unbiased reporting. Journal publication, a formalized platform for scientific discourse and dissemination of knowledge, should not be used as a marketing tool for off-label drug use.

Reporting biases such as those we describe here increase the likelihood that interventions will appear to be effective when they are not. Such biases can lead to the omission of negative findings in systematic reviews of intervention effectiveness and in evidence-based guidelines. For example, the 2005 Cochrane systematic review regarding the effectiveness of gabapentin for acute and chronic pain concluded that it is effective on the basis of published findings and should now be updated with the inclusion of unpublished information made available through litigation.

I believe that the article by Vedula et al is particularly important because it shows what appears to be systematic manipulation of the analysis and reporting of multiple clinical trials of the same drug (but for different indications) that had the effect of making the drug appear efficacious when it likely was not. Furthermore, the manipulation was concealed. The published research articles did not completely describe what the intended primary efficacy outcome variables were, did not provide results in terms of these variables, and instead provided results only in terms of variables that were chosen post-hoc as new primary outcome variables.

To address that latter point, I independently reviewed three of the research publications cited by Vedula et al.(2,3,4) All three were noted to have reported significant results favoring gabapentin in terms of a primary efficacy outcome variable that was not identified as such in the corresponding studies' original research protocols or reports (see the supplementary data provided with the New England Journal article.) Per my review, none of the three published articles offered any hint that what they reported as primary outcome variables were not the variables originally chosen in that capacity, nor did they identify what those original primary outcome variables were, or how comparisons made using them turned out.

The implications of the article by Vedula et al are very important. Hence, I was surprised that the article appeared without an accompanying editorial to discuss these implications, and that its publication did not generate much media interest.

So that gives me an opportunity to comment further.

One could start with the implications for evidence-based medicine. As noted above, a short description of the evidence-based medicine is medicine whose practice is informed by critical, rigorous review of the best available evidence from clinical research as revealed by systematic search of the published research literature, as well as by the clinician's understanding of biology and the medical and biopsychosocial context, and by the patient's own values. Evidence-based medicine depends on critical, rigorous review, but the review process is generally done under the assumptions that research publications honestly describe what was done and what its results were. The review process was never designed to detect dishonest reporting or find information that was deliberately concealed. Manipulation of research (design, analysis, and implementation), concealment of that manipulation, and outright suppression of research threaten the foundations of evidence-based medicine. Yet the article by Vedula et al is part of a growing body of evidence that such manipulation, concealment and suppression are widespread, and done to serve vested interests, often commercial.

That is a huge problem for proponents of evidence-based medicine, but also for physicians who want their practices to be based on science, for patients who want their care to be based on science, and for all those in society who see the advancement of medical science as a way to improve peoples' lives.

As senior author Professor Kay Dickersin noted in an interview with Bloomberg "The trouble is, as a scientist, the publication has always been held up to me as the truth. It's the scientific record. What this study indicated is we can't believe that record."

Furthermore, to be a bit more concrete, most physicians, patients, and policy makers depend on what appears to be honest clinical research to make decisions about individual care and health policy. Deliberate and deceitful manipulation of clinical research to favor sponsors' products has likely lead to excessive use of and payments for drugs and devices that are less effective than advertised, if not useless or dangerous. Thus, it is likely that such manipulation is partially responsible for ever increasing health costs and poor health outcomes.

Finally, we need to start thinking about how we can detect and compensate for manipulation of clinical research in the past, and deter such manipulation in the future. One possible deterrent would be, as was noted by Vedula et al, detailed clinical trials registries that contain complete information about trial protocols.  For this to be effective, there need to be mechanisms to assure compliance, and penalties for non-compliance.  Moreover, since clinical research is now global, the registries must have global scope, and enforced assurance of compliance must also be global.

Registries might decrease future manipulation and suppression of research.   No one has suggested, as far as I know, a systematic way to detect and correct for previous manipulation. It would require a major, global investigative effort to uncover manipulation, and it would be a major scientific and policy endeavor to reveal most suppressed research and correct most manipulations.

However, before anything is done, patients, physicians and policy makers must acknowledge and understand the problem.  Yet it seems that even discussing these may be topics that are very uncomfortable for some of us. The longer we shrink from addressing them, however, the worse will be the results for patients, physicians, science and society.

References


1. Vedula SS, Bero L, Scherer RW, Dickersin K. Outcome reporting in industry-sponsored tirals of gabapentin for off-label use. N Engl J Med 2009; 361: 1963-1971. Link here.


2. Mathew NT, Rapoport A, Saper J et al. Efficacy of gabapentin in migraine prophylaxis. Headache 2001; 41: 119-128. Link here.


3. Vieta E, Goikolea JM, Martinea-Aran A et al. A double-blind, randomized, placebo-controlled, prophylaxis study of adjunctive gabapentin for bipolar disorder. J Clin Psychiatr 2006; 67: 473-477.  Link here.


4. Caraceni A, Zecca E, Bonezzi C et al. Gabapentin for neuropathic cancer pain: a randomized controlled trial from the gabapentin cancer pain study group. J Clin Oncol 2004; 22: 2909-2917. Link here.

Omnicare, IVAX Settle

Settlements and kickbacks and corporate integrity agreements, oh my (to the tune of "lions and tigers and bears, oh my")

To quote the BusinessWeek version of the story:

A $112 million settlement involving alleged drug kickbacks that the Justice Dept. announced with the nation's largest nursing home pharmacy and a generic drug manufacturer on Nov. 3 is part of a wide-ranging investigation of suspected Medicaid fraud by the pharmaceutical industry.

Under Tuesday's settlement, Omnicare will pay $98 million plus interest to the federal government and a number of state Medicaid programs to settle allegations that it participated in kickback schemes with IVAX, J&J [Johnson & Johnson], and two nursing home chains. IVAX, a subsidiary of Israel's Teva Pharmaceutical Industries (TEVA), agreed to pay $14 million plus interest.

Omnicare and IVAX entered 'corporate integrity agreements' to establish new training and policies to prevent future problems. Neither company admitted any wrongdoing.

Here are some details of the alleged wrong-doing:

Omnicare is a publicly traded pharmacy benefit manager for long-term care facilities that operates in 47 states, the District of Columbia, and Canada. It had revenues of $6.3 billion in 2008.

According to the settlement, Omnicare allegedly received $8 million in payments from IVAX in 2000-04 to buy $50 million in generic drugs and recommend that physicians prescribe them to their nursing home patients. Omnicare entered the contract even though its outside counsel repeatedly warned it might violate the federal anti-kickback law, the government alleged in its complaint, filed in March. Omnicare also took payments from New Brunswick (N.J.)-based J&J from 1999 to 2004 to aggressively persuade doctors to prescribe Risperdal, an anti-psychotic drug, and discourage use of alternative medications, according to the settlement.

In addition, Omnicare allegedly paid $50 million to nursing home chains Mariner Health Care and SavaSeniorCare in 2004 to keep referring their Medicaid and Medicare patients to Omnicare for pharmacy services.

It is noteworthy that these activities went on despite repeated advice of at least one attorney:

According to the government's complaint, Omnicare again ignored its outside counsel's advice that the payment was illegal.

The activities also went on despite Omnicare's participation in a previous corporate integrity agreement.

This isn't the first time Omnicare has had to settle civil fraud complaints filed by the government. In 2006, Omnicare agreed to pay $102 million to settle Medicaid fraud cases in 43 states, without admitting wrongdoing, including a $52.5 million settlement with Michigan. One complaint accused Omnicare of switching two drugs from tablet to capsule form to boost Medicaid payments. Omnicare had to enter a five-year corporate integrity agreement.

As I have written again and again regarding many other cases that resulted in legal settlements or guilty pleas, the companies involved only need to pay fines, and no individual who performed, directed or approved unethical or illegal acts will suffer any negative consequences. I submit once again that such fines are viewed merely as costs of doing business by the affected companies, and do not deter future bad behavior.

For once, the coverage of this case included some opinions similar to mine:

The Office of Inspector General of the Health & Human Services Dept. has the authority to bar health-care companies from participating in the Medicaid, Medicare, and other federal health programs as a penalty for violating anti-fraud laws. That's a severe sanction given the huge size of those programs. The settlements with Omnicare and IVAX left open the possibility of exclusion.

Some experts say Omnicare should be barred as a repeat offender, to send a strong message to other pharmaceutical industry players that fraud will no longer be tolerated. 'If the government were really serious, they'd give Omnicare the death sentence,' said Erik Gordon, a business professor at the University of Michigan who follows the pharmaceutical industry. 'Then all the other players would say this isn't just the cost of doing business, this is a bet-the-company thing.'

West declined to comment on whether the Justice Dept. will recommended the exclusion of the two companies, saying only that his office works closely with the OIG's office on appropriate penalties.

[Patrick] Burns, with Taxpayers Against Fraud, said the government has been hesitant to exclude health-care companies for fraud, fearing it will be seen as overzealous. But he believes that's the wrong attitude. 'Doing business with the U.S. government is a privilege, not a right,' he said. 'I think Omnicare has abused the privilege.'

Finally, note that the description of this case suggested that the kickbacks had effects on physicians' prescribing and hence the use of specific drugs. The Justice Department's filing alleged that in return for the payment from IVAX, Omnicare tried to get physicians to prescribe that company's products, and that in return for the payment from J&J, Omnicare pushed them to prescribe the atypical anti-psychotic Risperdal. Thus the activities that went on this case could have lead to the use of inappropriate, useless or even harmful drugs by certain patients.

I submit that would-be health care reformers who want to improve care, reduce costs and improve access should advocate for real negative consequences for people who implement, direct or approve the various versions of fraud, kickbacks, and miscellaneous corruption and malfeasance we have discussed on Health Care Renewal.

By the way, it appears one of the members of Omnicare's Board of Directors is also a leader in academic health care.  She is Andrea R. Lindell, DNSc, RN, who is also Dean of the College of Nursing at the University of Cincinnati.  One would think that someone who thus boasts "the success of our students, faculty, staff and alumni who work together to promote excellence in education, research, service and practice" needs to keep a closer eye on the ethical aspects of her company's management.

Suppression of Clinical Trials of Sumatriptan

Correspondence to the Lancet two weeks ago revealed another instance in which clinical research studies that failed to provide results favorable to a sponsor's product were suppressed. [Tfeft-Hansen  PC. Unpublished clinical trials of sumatriptan. Lancet 2009; 374: 1501-2.  Link here.]

Sumatriptan, sold as Imitrex by GlaxoSmithKline, and now available generically, is a commonly used treatment for acute migraine headaches.  A Cochrane review from 2003 concluded that multiple clinical trials versus placebo showed that the drug is a safe and effective treatment of acute migraine [link here.]  A comparison of multiple guidelines for headache treatment noted considerable variability in how guidelines were developed, but that a number recommended sumatriptan as a first-line agent based apparently mainly on trials against placebo, while noting a lack of head-to-head comparisons among sumatriptan (and other triptans) and older, simpler treatments, like non-steroidal anti-inflammatory drugs (NSAIDs).  [Schuurmans A, van Weel C. Pharmacologic treatment of migraine: comparison of guidelines. Can Fam Physician 2005; 51: 838-843.  Link here.]

Tfelt-Hansen had written a review of treatment of migraine with a combination of ergotamine and caffeine, which included a single trial comparing that combination to sumatriptan.  He noted that the results of this trial appeared on "the homepage of the Swedish Medical Agency," but were not published in a peer-reviewed journal.  The trial suggested that sumatriptan was inferior to the combination. 

Tfelt-Hansen looked up this trial in the GlaxoSmithKline trial register.  Recall that this database was the source of information on unpublished trials of Avandia (rosiglitazone, GSK) that Dr Steven Nissen and colleagues meta-analyzed to suggest that Avandia may produce adverse cardiovascular effects (see post here).   Recall also that the registry was created as part of a settlement of a lawsuit by then New York Attorney General Elliot Spitzer that accused GSK of concealing clinical research unfavorable to its drug paroxetine (Paxil, GSK).  [Steinbrook R. Registration of clinical trials - voluntary or mandatory? N Engl J Med 2004; 351:1820-1822.  Link here.]

Tfelt-Hansen's main finding was that there were six trials comparing sumatriptan to other treatments, including paracetamol (acetaminophen) plus metaclopamide (2 trials), buclizine chloride, paracetamol and codeine (2 trials), ergotamine tartrate, cyclizine HCl, caffeine (1 trial), and ergotamine tartrate plus caffeine (1 trial).  In 3 trials, sumatriptan treated patients were not significantly more likely to have relief of their headaches within 2 hours.  In 1 trial, there was a non-significant trend favoring sumatriptan.  In two trials, sumatriptan was superior to the comparison.  In 4 trials, the rate of relief after sumatriptan treatment was 50% or less. 

Tfelt-Hansen concluded:

It is easy to understand why these RCTs were never published when sumatriptan was introduced: in only one of the oral trials did more than 50% of patients have headache relief (the primary efficacy measure) after sumatriptan 100 mg for the first attack treated (table), and in the RCT with rectal sumatriptan, the drug was found inferior to ergotamine. These findings would at the time have spoiled the very positive picture of sumatriptan as a new wonder drug for migraine.

Of course, this points out that health care corporations may regard clinical trials more as marketing tools than as science. We have discussed numerous instances in which trials that did not show commercial sponsors' products in a favorable light were suppressed by these sponsors.

Individual trials only at best produce approximations of the truth about the drugs or devices they compare. Trials may be positive due to chance alone when the test or treatment under study actually has no good effects. Post-hoc suppression of "negative" trials therefore may exaggerate the benefits (and safety) of tests or treatments. Physicians and patients who try to uphold the ideals of evidence-based medicine, and base decisions on the best possible evidence can be misled when evidence unfavorable to vested interests is systematically suppressed. Suppression of evidence unfavorable to vested interests may lead to excess use of tests and treatments that really are less beneficial or more risky than the published evidence suggested, and to willingness to pay exaggerated prices for such tests and treatments. Thus suppression of evidence can lead to excess costs and bad outcomes.

Also, as we have said before, suppression of results of clinical research that are unfavorable to the vested interests of research sponsors violates the trust of research subjects.  Research subjects are often assured that their participation is for the benefit of science and health care.  Suppressing results unfavorable to vested interests distorts science and makes health care more dysfunctional.

Evidence that is purposefully suppressed is by definition hard to find. Nonetheless, we have seen several recent examples in which suppressed evidence was later revealed, and when combined with existing evidence, showed that previously hyped treatments were really not as safe and effective as was thought.  In particular, the suppression by various drug companies of evidence unfavorable to new anti-depressants they were marketing has generated some discussion (see post here).

This parade of examples suggests that stronger measures are needed to assure that clinical research is not suppressed due to the vested interests of research sponsors.  One seemingly radical, but increasingly plausible approach would ban corporations that sell health care products or services from influencing clinical research done to evaluate those products.  Would be health care reformers who really want to improve outcomes, improve access and decrease costs might want to think about how to make the evidence available about the outcomes of health care interventions more honest.

Boston Scientific to Plead Guilty (of Suppressing Information about Failure-Prone Defibrillators)

In the early days of Health Care Renewal (2005-2006) we posted several times about allegations that Guidant hid information about defects in the implantable cardiac defibrillators (ICDs) the company manufactured.  As we noted in early 2005 here, Guidant executives allegedly knew that ICDs made from 2000-2002 were at risk for short-circuiting and failing, thus making them unable to deliver potentially life saving electrical shocks meant to prevent cardiac arrests, but the company only revealed the problem in 2005.  By failing to notify physicians and the public, Guidant executives let expensive and profitable, but potentially useless devices to continue to be implanted, potentially increasing the risk of sudden death for the patients who received them.  Then here we noted reports that Guidant continued to ship failure-prone devices even after it had designed and started to manufacture new ICDs that were supposed to be less likely to fail.  By June, 2005 we posted that Guidant had recalled thousands of ICDs, including models that were previously not identified as likely to fail.  Later that year, the case rated an article by Robert Steinbrook in the New England Journal of Medicine.  Towards the end of 2005, we noted that Eliot Spitzer had sued Guidant for fraud.  At the end of the year, more information appeared, suggesting that Guidant knew the ICDs were flawed, but continued to sell them.  Still more appeared early in 2006.  Then the business media became interested in the bidding war between Johnson and Johnson and Boston Scientific for Guidant, provoking a bit more interest in the tale of the suppression of data about the flawed ICDs.

And then there was silence.  The story of the suppressed information about the defective defibrillators became old news, as did the story of the merger between Boston Scientific and Guidant.  The story vanished, nothing more happened, until last week

A lone echo from this story from what now seems long ago was heard, as reported by Bloomberg,

Boston Scientific Corp. agreed to pay $296 million to settle a U.S. Justice Department investigation into its Guidant unit’s handling of heart devices and restated third-quarter results to show a loss.

Guidant will plead to two criminal misdemeanors for failing to properly alert the U.S. Food and Drug Administration about problems with some of its implantable defibrillators, Boston Scientific said today in a statement. The probe concerned product advisories sent by Guidant before its acquisition by Boston Scientific in April 2006, the parent company said.

So even though Boston Scientific's now subsidiary Guidant will plead guilty to a crime involving suppression of information about the flaws in its defibrillators, the current CEO of Boston Scientific denied anyone did anything wrong:

'Guidant and its employees acted in good faith and believed they complied with applicable laws and regulations,' Boston Scientific Chief Executive Officer Ray Elliott said in the company’s statement. 'We elected to resolve this matter so we could put it behind us and devote our full energies and resources to developing our innovative technologies.'

I guess it's not hard to put a little matter of criminal conduct behind a big health care corporation and its leaders when the only downside of pleading guilty is a fine paid seven years after the criminal conduct occurred.  Moreover, that fine that will come out of the company treasury, and its impact will thus be spread among stock-holders, employees, and customers, not targeted at those who performed, directed or approved the acts that lead to the guilty plea.

Although the Bloomberg report was more detailed than others I found, none mentioned that the information that was concealed back in the day was about the failure of an expensive device that was supposed to be life-saving, and whose failure might doom some of its recipients to an early death.  Anyone reading these late 2009 articles would get a sense that Guidant personnel were guilty of some technical reporting violations, not of withholding information that supposed life-saving treatments might be useless.

As in the case of many other cases that resulted in legal settlements or guilty pleas, the company involved only needs to pay a fine, and no individual who performed, directed or approved unethical or illegal acts will suffer any negative consequences.  I submit once again that such fines are viewed merely as costs of doing business by the affected companies, and do not deter future bad behavior.

In this vein, note that in 2005, Boston Scientific agreed to a $74 million settlement of charges that it knowingly sold a defective coronary artery stent system (see post here), which did not deter the company from merging with Guidant. 

This case also demonstrates how the anechoic effect continues.  Bad behavior by large health care organizations still gets little notice, and when it is noticed, its real clinical and human effects are discounted. 

Real health care reform would address how leaders of health care organizations can continue to act with impunity even when their actions can lead to sickness, disability, and death. 

Academic Freedom and ED EHR's Down Under: Another Update and a Welcome Development

In "Academic Freedom and ED EHR's Down Under: An Update" I wrote about the disputed essay on electronic health record (EHR) problems in the Australian state of New South Wales (NSW) by medical informatics professor Dr. Jon Patrick, Health Information Technologies Research Laboratory (HITRL), University of Sydney.

The essay was entitled "A Critical Essay on the Deployment of an ED Clinical Information System ‐ Systemic Failure or Bad Luck?"

I am happy to report that an updated version of the essay, version 5, is now available from Dr. Patrick's university web site at http://www.it.usyd.edu.au/~hitru/index.php?option=com_content&task=view&id=91&Itemid=146 . It can be downloaded from the icon at Item 6.

This is a welcome development.

The essay is now labeled as an Op-Ed (Opinion Editorial).

-- SS

The Kelo Case Redux Once More: Pfizer Pulls Out and the "Carefully Formulated" Development Plan Collapses

Four years ago we posted (here, here and here) about the controversial US Supreme Court decision in the Kelo case. Most discussion of the case at the time focused on individual property rights vs the power of the government to promote economic development, but the case had an important health care angle.

Briefly, the case centered on the taking of private property, including a house owned by Susette Kelo, by a not-for-profit organization, the New London (Connecticut) Development Corporation (NLDC) given the power of eminent domain by the New London city government. While the ostensible rationale for the taking was economic development, the action appeared to have been at the behest of Pfizer Inc, the world's largest pharmaceutical company, which had built a research and development facility in the city, and wanted a suitably upscale and sanitized environment for its workers.

As we previously posted, the NLDC's leadership had multiple conflicts of interest that involved ties to Pfizer. One board member was a Pfizer vice-president. The board president was married to another Pfizer vice-president. Pfizer wanted the part of New London that included Kelo's house made more attractive to complement its new research facility. The husband of the NLDC president had said, "Pfizer wants a nice place to operate. We don't want to be surrounded by tenements."

Kelo's and other property owners' protest of the taking went all the way to the US Supreme Court. As we posted here, the Court decided against the property owners by a 5-4 vote. Justice John Paul Stevens wrote for the majority that the city's "determination that the area was sufficiently distressed to justify a program of economic rejuvenation is entitled to our deference. The city has carefully formulated an economic development plan that it believes will provide appreciable benefits to the community, including - but by no means limited to - jobs and increased revenues." This majority opinion is important, because the Fifth Amendment to the US Constitution provides "nor shall private property be taken for public use without just compensation." Many had interpreted this provision to mean that eminent domain could only be used to take property for public use, e.g., to build a road or a public school, but not for private purposes, like building upscale waterfront developments.

Two months ago, we posted on how the supposedly "carefully formulated" development plan had fallen apart.  The land on which the Kelo house stood had never been developed, and remained a weedy lot.
 
This week, the (New London) Day reported:

Eight years after opening its state-of-the-art global research-and-development headquarters in New London, Pfizer Inc. announced Monday it will close the nearly $300 million complex within the next two years and consolidate local operations into its Groton campus.

Why did Pfizer decide to close the facility?

Pfizer earlier this year said nearly 20,000 jobs would be cut as a result of its merger with the New Jersey-based Wyeth. The company said Monday that about 15 percent of its overall R&D work force would be cut as part of that downsizing.

The result apparently will be the complete dissolution of the "carefully formulated" development plan.

The announced closing of the New London site came as a blow to a city that had counted on Pfizer to help revive its fortunes.

The loss of Pfizer as a keystone business in New London could put in further jeopardy the Fort Trumbull development that started in conjunction with Pfizer's move into the city but has left little but flattened buildings and eminent-domain angst in its wake.

So, the unfortunate Kelo case has become a vivid demonstration how badly government does when it partners with businesses and tries to pick corporate winners and losers.  Unfortunately, it seems that much of what passes for US health care policy is such "corporate socialism."  As we said before, instead of trying to pick corporate winners and losers, government would do better to act like a combination of an honest policeman on the beat, deterring and punishing dishonest behavior, and in impartial referee, trying to make sure everyone is playing the game honestly. But no doubt government officials used to mingling with the corporate superclass would not be comfortable in the roles of honest cop or impartial referee.

See also comments on the Volokh Conspiracy blog.  Hat tip to the PharmaLot blog.